CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2
CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2
复制标题
CHD1L通过调节METAP2促进EOC细胞侵袭和转移
DOI：
10.7150/ijms.48615
复制
发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Yang, Guo-Fen
中科院分区：
文献类型：
--
作者：
He, Wei-Peng;Guo, Yun-Yun;Yang, Guo-Fen
染色体结构域解旋酶DNA结合蛋白1样基因（Chromodomain helicase DNA binding protein 1-like，CHD 1 L）在人肝细胞癌中起致癌作用。我们曾报道CHD 1 L过表达与上皮性卵巢癌（EOC）的转移进程显著相关，并可能预示EOC患者的不良预后。然而，CHD 1 L在EOC中发挥作用的潜在致癌机制仍不清楚。为了阐明CHD 1 L的致癌功能，我们进行了一系列体外试验，在EOC细胞系（HO 8910，A2780和ES 2）中测定CHD 1 L外源性过表达和沉默的影响。采用实时荧光定量PCR和Western blotting方法分析CHD 1 L在EOC侵袭和转移过程中的潜在下游靶点。在卵巢癌细胞系HO 8910中，CHD 1 L的异位过表达显著诱导了癌细胞的体外侵袭和转移能力。相反，在卵巢癌A2780和ES 2细胞系中，使用shRNA敲低CHD 1 L抑制细胞体外侵袭。我们还证实了甲硫氨酰氨基肽酶2（METAP 2）是EOC中CHD 1 L的下游靶点，并且我们发现EOC组织中CHD 1 L和METAP 2的表达之间存在显著的正相关（P<0.05）。我们的研究结果表明，CHD 1 L通过调节METAP 2表达在诱导EOC癌细胞侵袭和/或转移中起潜在作用，并表明CHD 1 L抑制可能为人类EOC的治疗干预提供潜在靶点。
Chromodomain helicase DNA binding protein 1-like (CHD1L) gene has been proposed to play an oncogenic role in human hepatocellular carcinoma. Previously we reported that CHD1L overexpression is significantly associated with the metastasis proceeding of epithelial ovarian cancer (EOC), and may predict a poor prognosis in EOC patients. However, the potential oncogenic mechanisms by which CHD1L acts in EOC remain unclear. To elucidate the oncogenic function of CHD1L, we carried out a series of in vitro assays, with effects of CHD1L ectogenic overexpression and silencing being determined in EOC cell lines (HO8910, A2780 and ES2). Real-time PCR and Western blotting analyses were used to identify potential downstream targets of CHD1L in the process of EOC invasion and metastasis. In ovarian carcinoma HO8910 cell lines, ectopic overexpression of CHD1L substantially induced the invasive and metastasis ability of the cancer cells in vitro. In contrast, knockdown of CHD1L using shRNA inhibited cell invasion in vitro in ovarian carcinoma A2780 and ES2 cell lines. We also demonstrated that methionyl aminopeptidase 2 (METAP2) was a downstream target of CHD1L in EOC, and we found a significant, positive correlation between the expression of CHD1L and METAP2 in EOC tissues (P<0.05). Our findings indicate that CHD1L plays a potential role in the inducement of EOC cancer cell invasion and/or metastasis via the regulation of METAP2 expression and suggests that CHD1L inhibition may provide a potential target for therapeutic intervention in human EOC.